High Titers Of Anticardiolipin Antibodies Research Articles

Pregnancy failure in patients with obstetric antiphospholipid syndrome with conventional treatment: the influence of a triple positive antibody profile.

Conventional treatment of obstetric antiphospholipid syndrome fails in approximately 20-30% of pregnant women without any clearly identified risk factor. It is important to identify risk factors that are associated with these treatment failures. This study aimed to assess the impact of risk factors on pregnancy outcomes in women with obstetric antiphospholipid syndrome treated with conventional treatment. We carefully retrospectively selected 106 pregnancies in women with obstetric antiphospholipid syndrome treated with heparin + aspirin. Pregnancy outcomes were evaluated according to the following associated risk factors: triple positivity profile, double positivity profile, single positivity profile, history of thrombosis, autoimmune disease, more than four pregnancy losses, and high titers of anticardiolipin antibodies and/or anti-βeta-2-glycoprotein-I (aβ2GPI) antibodies. To establish the association between pregnancy outcomes and risk factors, a single binary logistic regressions analysis was performed. Risk factors associated with pregnancy loss with conventional treatment were: the presence of triple positivity (OR = 5.0, CI = 1.4-16.9, p = 0.01), high titers of aβ2GPI (OR = 4.4, CI = 1.2-16.1, p = 0.023) and a history of more than four pregnancy losses (OR = 3.5, CI = 1.2-10.0, p = 0.018). The presence of triple positivity was an independent risk factor associated with gestational complications (OR = 4.1, CI = 1.2-13.9, p = 0.02). Our findings reinforce the idea that triple positivity is a categorical risk factor for poor response to conventional treatment.

Lupus anticoagulant, warfarin, and alternative laboratory monitoring of anticoagulation

A 53 year old woman was evaluated for recurrent native and prosthetic mitral valve thromboembolism in the setting of antiphospholipid antibody syndrome. In 1989, at age 30 years, she suffered a thromboembolic stroke and was diagnosed with antiphospholipid antibody syndrome for which long-term warfarin therapy was prescribed. She was subsequently assigned a goal international normalized ratio (INR) of 2.5–3.5. In 2008, at age 49 years, she was diagnosed with mitral valve stenosis and underwent mitral valve replacement (29 mm Carbomedics prosthesis). Pathology was consistent with nonbacterial thrombotic endocarditis involving a fibrotic and focally calcified mitral valve. After valve replacement, the target INR range was increased to 3.0–4.0. Nine months later, she developed thrombosis of the prosthetic mitral valve and required redo valve replacement surgery (27 mm St. Jude Biocor). Postoperatively, she developed heparin induced thrombocytopenia (HIT) for which she received argatroban while transitioning to warfarin. Her target INR range was subsequently increased to 3.5–4.5. In 2012, she developed recurrent prosthetic mitral valve thrombosis despite being mostly therapeutic(INR 3.5–4.5) and at times supra-therapeutic with INR monitoring. Transesophageal echocardiogram confirmed an 8 mm thick layer of organized thrombus encasing each of the prosthetic mitral valve leaflets with severe valvular stenosis. Laboratory testing upon admission revealed a prothrombin time (PT) of 101.7s (INR 11.1). Simultaneously measured chromogenic factor X activity was 20 % (therapeutic range 20–35 %) and factor II activity was 14 % (normal reference range 75–145 %), confirming adequate anticoagulation at that time. A third mitral valve replacement procedure was pursued (27 mm Hancock II bioprosthesis) and she was yet again restarted on warfarin postoperatively. Initial special coagulation testing done at our institution in 1989 established the presence of a lupus anticoagulant (LAC). This diagnosis was subsequently confirmed on four occasions (1995–2012). Prior to 2004, the LAC assays were performed using the dilute Russel viper venom time (DRVVT) assay kit from American Diagnostica (Stamford, CT). After 2004, the DRVVT assay was performed using the kit from Precision Biologics (Dartmouth, NS, Canada) following the manufacturer’s instructions. She had a persistently high titer of anticardiolipin antibodies (IgG and IgM) as well. Her baseline prothrombin PT (11.3s) and INR (1.1), were normal and remained so until 2012, when measured during brief interruptions of warfarin anticoagulation (six occasions; 1995–2011). Prior to 2009, the PT assay was performed with Innovin (Siemens, New York, NY formerly Dade Behring, Deerfield, IL). Beginning in 2009, the PT was performed with Recombiplastin 2G (Instrumentation Laboratories, Bedford, MA). The temporal trends in INR and chromogenic factor X activity are shown in Fig. 1. Since INR differences are much larger at low factor activities than at high activities, we compared the log INR with the factor activities. Log INR did not correlate well with chromogenic factor X activity (Fig. 2a, r = 0.32) and factor II (Fig. 2b, S. S. Ketha (&) R. D. McBane W. E. Wysokinski Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Gonda 4-130 (VM), 200 First St. SW, Rochester, MN 55905, USA e-mail: Ketha.Siva@mayo.edu

THU0170 The effect of the antiphospholipid syndrome (APS) on survival in 679 patients with sle: A prospective study

ObjectivesTo study the effect of the antiphospholipid syndrome (APS) on survival in Chinese patients with SLEMethodsA cohort of 679 southern Chinese patients who fulfill at least 4 of the ACR...

The role of paraoxonase in the formation of atherosclerotic changes in the vessels of patients with antiphospholipid syndrome

As a result of studies carried out by the authors a significant reduction of the serum paraoxonase activity in a Ukrainian population of patients with antiphospholipid syndrome (APS) has been demonstrated. The main factors that affect the enzyme level were the male gender, age, arterial hypertension, tobacco smoking, abnormalities of lipid metabolism. The course of the disease and obesity did not play a significant role. Cause-and-effect relationships between a low enzymatic activity in patients with APS and the presence of high titers of anticardiolipin antibodies and beta-2 glycoprotein 1 antibodies has been established. A reduction of paraoxonaze level is a predictor of an early development of structural and functional changes in the blood vessels of patients with APS.

Evaluation of the Presence of Hereditary and Acquired Thrombophilias in Brazilian Children and Adolescents With Diagnoses of Portal Vein Thrombosis

The aim of this study was to describe the prevalence of main hereditary thrombophilias, Janus kinase 2 (JAK2) V617F mutation, antiphospholipid antibody syndrome (APS), and hyperhomocysteinemia in Brazilian children and adolescents diagnosed with portal vein thrombosis (PVT) without associated hepatic disease. A cross-sectional study was carried out with 32 children with PVT in accompaniment at Hospital das Clínicas of the Universidade Federal de Minas Gerais from January 1990 to July 2011. Laboratory evaluation of thrombophilias was performed from September 2010 to July 2011. Thirty-two patients were evaluated; 59% were boys. Median age at diagnosis was 2.4 years. Mean time of patients' accompaniment was between 4.7 and 5.2 years. The presence of hereditary and acquired thrombophilias occurred in 34.4% of patients, and 9 of them also showed other risk factors in the previous history evaluation. Risk factors were absent in the previous history of 18 patients (56.3%). Two patients showed persistent high titres of anticardiolipin antibodies. Hyperhomocysteinemia was not observed. One patient was heterozygous for factor V Leiden and prothrombin G20210A mutation (3.1%). Eleven patients (34.4%) showed heterozygous methylenetetrahydrofolate reductase (MTHFR) C677T, and no patient had the JAK2V617F mutation. Even after investigation of main hereditary and acquired thrombophilia, PVT remains without apparent cause in most patients. Nevertheless, association of local and systemic risk factors seems to be important also in the pediatric age group. Therefore, despite the low prevalence, a complete investigation, which includes both hereditary and acquired thrombophilias, may be necessary.

Hereditary Spherocytosis (HS) Associated with a Heterozygous MTHFR C677T Mutation and with Elevated Anticardiolipin Antibodies.

Abstract 5069 BackgroundHereditary spherocytosis (HS) is a spectrum of inherited erythrocyte membrane defects that result in hemolysis and varying degrees of anemia, usually not associated with increased thrombotic risk. However, there is some concern about post-splenectomy thrombocytosis, since both arterial and venous thromboembolic events have been reported in patients splenectomized for HS.A review of the medical literature revealed only a few cases of thrombosis associated with pregnancy and hereditary spherocytosis, and none of them had methyl tetrahydrofolate reductase (MTHFR) mutations or the presence of elevated anticardiolipin antibodies (both considered risk factors for thromboembolic disease). MethodsCase report ResultsA 34-year-old Caucasian female with history of hereditary spherocytosis and splenectomy at age five, underwent evaluation for infertility. The patient was found to have a high titer of anticardiolipin antibodies and the presence of heterozygosity for the MTHFR C677T mutation. She denied any personal or family history of deep venous thrombosis. Subsequently the patient became pregnant. Because the combination of thrombophilic states appears to increase the risk of thromboembolic events, it was decided to start the patient prophyllactically with oral aspirin 81 mg daily, Foltx® (Folic acid 2.5 mg, cyanocobalamin 2000 mcg, and pyridoxine hydrochloride 25 mg), and heparin 5000 mg subcutaneously twice a day. On her most recent evaluation, at 26 weeks of pregnancy, no medical or obstetric problems have been observed. ConclusionOur case illustrates an unusual combination of thrombophilic states. Further studies are needed to evaluate the clinical significance of this association. DisclosuresNo relevant conflicts of interest to declare.

Pathogenic natural anti-cardiolipin antibodies: the experience from monoclonal gammopathy.

Anti-cardiolipin antibodies (ACA) were detected in 19% of sera from patients with monoclonal gammopathies (MG). ACA were purified from the sera of patients with MG. One of the IgG-ACA was found to be monospecific with high affinity for cardiolipin, and to carry a pathogenic ACA Id (1.10). Active immunization of naive BALB/c mice with the purified IgG-ACA was followed by production in the mice of sustained high titres of ACA, associated with prolonged activated partial thromboplastin time (APTT) (61 +/- 14s versus 31 +/- 2s in control mice; P < 0.001) and thrombocytopenia (468,000 +/- 224,000/mm3 versus 994,000 +/- 92,000/mm3 in controls; P < 0.001). The titres of other autoantibodies (e.g. anti-DNA, anti-histones), although being high after immunization, decreased rapidly and were undetected after 1 month following the boost injection. The mice immunized with the IgG-ACA exhibited low fecundity (36% of mice became pregnant versus 62% observed in the group immunized with control IgG). The pregnant mice had increased resorption rate (the equivalent of fetal loss in the human) of 52 +/- 8% (versus 5 +/- 4% in the control group). The mean (+/- s.d.) embryo and placental weights in mice with anti-phospholipid syndrome (APLS) were significantly lower compared with the mice injected with control IgG (682 +/- 304 mg and 102 +/- 12 mg versus 1303 +/- 105 mg and 145 +/- 8 mg, respectively; P < 0.001). Serum monoclonal immunoglobulins having autoantibody activity may be regarded as an expansion of clones producing natural autoantibodies. Our results confirm the pathogenic role of natural ACA in the pathogenesis of the anti-phospholipid syndrome.

Polyarteritis Nodosa Complicated by Antiphospholipid Syndrome

Polyarteritis nodosa is a necrotizing vasculitis of small and medium-sized arteries that spares the smallest blood vessels (arterioles, venules, and capillaries). Antiphospholipid syndrome is an autoimmune disorder characterized by venous or arterial thrombosis and/or by fetal losses, associated with antiphospholipid antibodies. The association of both diseases is infrequent. This case report discusses a male patient with a diagnosis of polyarteritis nodosa who, after 7 years of being diagnosed with vasculitis, showed ischemic lesions in his legs associated with high titers of anticardiolipin antibodies, along with angiographic and histologic evidence of thrombosis. Despite immunosuppressive and anticoagulant therapy, his lesions progressed, and both legs had to be amputated.

Benign intracranial hypertension associated to blood coagulation derangements

BackgroundBenign Intracranial Hypertension (BIH) may be caused, at least in part, by intracranial sinus thrombosis. Thrombosis is normally due to derangements in blood coagulation cascade which may predispose to abnormal clotting activation or deficiency in natural inhibitors' control. The aim of the study is to examine the strength of the association between risk factors for thrombosis and BIH.Patients and methodsThe incidence of prothrombotic abnormalities among a randomly investigated cohort of 17 patients with BIH, was compared with 51 healthy subjects matched for sex, age, body mass index, height and social background.ResultsThe number of subjects with protein C deficiency was significantly higher in patients than in controls (3 vs 1, p < .001; Fisher Exact Test). Moderate to high titers of anticardiolipin antibodies (β2-Glycoprotein type I) were found in 8 out of 17 patients.Increased plasma levels of prothrombin fragment 1+2, fibrinopeptide A (FPA), and PAI-1 were demonstrated in patients group (5.7 ± 1.15 nM vs 0.45 ± 0.35 nM; 8.7 ± 2.5 ng/mL vs 2.2 ± 1.25 ng/mL; 45.7 ± 12.5 ng/mL vs 8.5 ± 6.7 ng/mL, respectively; p < .001; Fisher Exact Test). Gene polymorphisms for factor V Leiden mutation, prothrombin mutation 20210 A/G, MTHFR 677 C/T, PAI-1 4G/5G, ACE I/D were detected in 13 patients.DiscussionIn agreement with other authors our data suggest a state of hypercoagulability in BIH associated with gene polymorphisms. Our findings also showed that mutations in cardiovascular genes significantly discriminate subjects with a BIH history. The association between coagulation and gene derangements, usually regarded to as cryptogenic, may suggest a possible pathogenetic mechanism in BIH. So, a prothrombotic tendency may exist that would, at least in part, explain some cases of BIH.Although based on a small population, these findings raise the exciting possibility of using these haemostatic factors as markers for selecting high-risk subjects in BIH disease.

Combined Oral Contraceptives in Women With Systemic Lupus Erythematosus

The Oral Contraceptives part of the Safety of Estrogens in Lupus Erythematosus National Assessment (OC-SELENA) study was a prospective, randomized, double-blind trial carried out at 15 U.S. centers that examined the effects of oral contraceptives on disease activity in 183 premenopausal women with systemic lupus erythematosus. Initially, disease was inactive in 76% of participants and active but stable in the remaining 24%. Participants were assigned to receive 35 μg triphasic ethinyl estradiol plus 0.5, 0.75, or 1 mg norethindrone, or placebo, for 12 28-day cycles. None of the subjects had moderate to high titers of anticardiolipin antibodies, lupus anticoagulant, or a history of thrombosis. Just over one third of patients in each group failed to comply throughout the 12-month study. Only seven of 91 women given oral contraceptives and seven of 92 placebo recipients had a severe flare of disease during the study. Two flares in the active treatment group occurred when the study drug was omitted. On Cox proportional-hazards analysis, the relative risk (RR) of a severe flare occurring during OC treatment, compared with placebo, was 0.93 (95% confidence interval [CI], 0.33–2.65). The estimated difference was less than the maximum clinically acceptable difference. Participants in both groups who had active disease at the outset were likelier than those whose disease was inactive to have a severe flare. The estimated RR, adjusted for treatment, was 3.5 (95% CI, 1.23–9.99). Rates of moderate or mild flares were similar in the treatment and placebo groups. The likelihood of having at least one flare of any degree during 12 months of follow up was 76% for actively treated patients and 69% for those in the placebo group (RR, 1.09; 95% CI, 0.76–1.55). One OC-treated patient had deep venous thrombosis (DVT) and one had a clotted graft. In the placebo group, there was one case each of DVT, ocular thrombosis, and superficial thrombophlebitis, and one woman died after the trial ended. These findings endorse the use of oral contraceptives, including estrogen, as a birth control measure by women having inactive or active but stable systemic lupus erythematosus. These patients are at relatively low risk of developing thrombosis.

Antiphospholipid syndrome in patients with systemic lupus erythematosus treated by autologous hematopoietic stem cell transplantation

AbstractSystemic lupus erythematosus (SLE) is the most common disease associated with antiphospholipid syndrome (APS). We, therefore, evaluated 46 patients with refractory SLE treated by autologous hematopoietic stem cell transplantation (HSCT) for a history of APS prior to transplantation. The prevalence of SLE-related APS in our patient population was 61% (28 of 46 patients with refractory SLE). Nineteen of 28 patients with APS had lupus anticoagulant (LA) or high titers of anticardiolipin antibodies (ACLAs), either immunoglobulin (Ig)G or IgM, when evaluated at study entry. Six of 8 evaluable LA+ patients became and remained LA–; 5 of 7 initially ACLA IgG+ patients and 9 of 11 ACLA IgM+ patients demonstrated normalization of ACLA titers when followed after HSCT. Eighteen of 22 patients refractory to chronic anticoagulation discontinued anticoagulation therapy a median of 4 months after transplantation; 78% of them remained free of thrombotic events and in complete SLE remission for up to 78 months (median, 15 months) after HSCT. There was no treatment-related mortality. Autologous HSCT may be performed safely in patients with APS and appears to be effective therapy for eliminating ALPAs and preventing thrombotic complications in patients with SLE.

Antiphospholipid Syndrome in Patients with Systemic Lupus Erythematosus Treated by Autologous Hematopoietic Stem Cell Transplantation.

The association of antiphospholipid antibodies (APLA) with either vascular thrombosis or fetal morbidity is known as the antiphospholipid syndrome (APS). Since systemic lupus erythematosus (SLE) is frequently associated with APS, we analyzed 44 patients with severe and refractory SLE involved in a larger study of autologous hematopoietic stem cell transplantation (HSCT) utilizing cyclophosphamide and antithymocyte globulin (ATG) conditioning to determine the efficacy of this treatment in eliminating APLA and preventing recurrent thrombi. The prevalence of SLE-related APS in our patient population was 63% (45% met Sapporo criteria for definite APS, and 18% had history of APLA positivity with associated clinical APS features). Nineteen patients with APS had lupus anticoagulant (LA) and/or high titers of anticardiolipin antibodies (ACLA) at the entry into study. Ten patients were positive for LA. Fourteen patients showed elevated titers of ACLA, IgG and/or IgM. When followed for up to 30 months after autologous HSCT, 70% of initially LA-positive patients became and remained negative for anticoagulant. 79% demonstrated normalization of ACLA titers during maximum of 28 months follow-up. 64% of patients refractory to chronic anticoagulation regimen were able to discontinue from anticoagulation therapy at average of 6 months post-transplant and remained thrombotic events-free and in complete SLE remission for up to 78 months after HSCT. There was no treatment-related mortality or severe adverse events, including stem cell engrafment-related hematological complications or overhelming bacterial, fungal or viral infection, in any of the 28 SLE-related APS patient. Autologous hematopoietic stem cell transplantation may be performed safely and appears to be effective therapy for eliminating SLE-related APLA and preventing further thrombotic events.

Clinical and ethnic characteristics of stroke in an Israeli population: a study in a community hospital population

Background: Stroke mainly affects the older population, although it has also been reported in younger patients. In this study, we focused on patients 65 years of age or younger with stroke. Methods: The files of three patient populations were studied: 93 patients aged 65 years or younger with stroke (group A), 93 patients older than 65 with stroke (group B), and 604 patients without stroke representing the general population of patients admitted to our service during January 2000 (group C). We reviewed the patient files and compared patient characteristics, epidemiological features, clinical picture,imaging findings, and coagulation tests. Results: Overall, 318 patients were studied. The mean age of group A was 55 years compared to 77 years in group B and 71 years in group C. In both stroke groups (A and B), the male: female ratio was 2:1, in contrast with a balanced ratio in group C. Most of the patients in group A (63%) were of Sephardic origin compared to 39% in group B ( P=0.002) and 30% in group C. The clinical picture in both stroke groups (A and B) was similar. The risk factor smoking was reported by 45% in group A and by only 29% in group B ( P=0.034). Hypertension, diabetes mellitus, and hyperlipidemia were evenly prevalent in both stroke groups. The coagulation system was studied in the “young” patients (group A): hyperhomocysteinemia was found in 37%, high titers of anticardiolipin antibodies in 35%, low levels of antithrombin III in 13%, protein C deficiency in 5%, and activated protein C resistance (APCR) in 4%. Overall, 49% of the patients from group A were found to have coagulation abnormalities. Conclusions: We found in our study that the younger patient with stroke tends to be a Sephardic male with the classical risk factors as well as a history of smoking and coagulopathy. These findings suggest strict medical supervision and primary prophylaxis. This work also lays the basis for a prospective, interventional trial with younger patients.

Non-lupus nephropathy associated with antiphospholipid antibodies

Renal biopsy was performed in a 12-year-old girl with hematuria and proteinuria which was first detected at the age of 7, and the findings were the mesangial proliferative glomerulonephritis with IgG and C3 deposits. The routine blood examination for the biopsy disclosed the presence of the prolonged activated partial thromboplastin time and the biological false positive reaction in the syphilis test. These results led us to the further investigation, which revealed the presence of high titers of anticardiolipin antibodies. Since this girl presented no extra-renal symptoms of systemic lupus erythematosus (SLE) and had negative serologic tests for SLE, we hypothesize that her nephritis is closely related to antiphospholipid antibodies.

Multifactorial thrombotic-type microangiopathy with skin ulcers and hepatitis C infection

The case of a patient with hepatitis C virus infection who presented with symmetric ulcers of the legs is reported. She was found to have type III mixed cryoglobulinemia, high titers of anticardiolipin antibodies, lupus anticoagulant, and a free protein S deficiency. To our knowledge, this is the first reported case of such an association. The role of these factors in the pathogenesis of skin lesions in the setting of hepatitis C virus infection is discussed.

Síndrome antifosfolípido con infarto de miocardio y afectación valvular aórtica

The primary antiphospholipid syndrome is a disorder which is characterized by: arterial and/or venous thrombosis, thrombocytopenia, recurrent fetal loss and high plasma levels of antiphospholipid antibodies. Valvular involvement is associated with arterial thrombosis and the most frequent manifestation is regurgitation. We report the case of a young male with primary antiphospholipid syndrome and previous cerebrovascular thrombosis hospitalized for subacute myocardial infarction. Coronary angiography revealed right and left anterior descendent coronary artery stenosis, the latter being successfully recanalized by direct percutaneous transluminal coronary angioplasty. Transthoracic echocardiography demonstrated aortic valve involvement with predominant regurgitation and transesophageal echocardiography detected valve excrescences on the aortic leaflets. Laboratory study demonstrated thrombocytopenia, prolonged activated partial thromboplastin time and high titers of anticardiolipin antibodies. Oral anticoagulation therapy was started. Thrombotic events have not recurred after three months of follow-up.

Structural characterization and optimization of antibody-selected phage library mimotopes of an antigen associated with autoimmune recurrent thrombosis.

The presence of high titers of anti-cardiolipin antibodies (ACA's) of autoimmune origin, which are known to bind to plasma beta2-glycoprotein I (aka apolipoprotein H), correlates clinically with autoimmune recurrent thrombosis. Soluble beta2-glycoprotein I binds to solid-phase ACA (immobilized on a surface plasmon resonance chip) with a Kd of 1.4 microM, but if the reactants are reversed and beta2-glycoprotein I is on the solid-phase support, then the Kd is 52 nM. This 27-fold difference in affinity reflects the avidity/entropic advantage obtained for an antibody binding to an antigen that is made multivalent because it is attached to a solid phase. A mimotope of this antigen, selected from a phage display peptide library screen with an ACA, has been shown to bind to solid-phase ACA as a phage, using surface plasmon resonance. This peptide is representative of the motif from 37 peptides obtained in a previously reported phage library screen with this ACA (1). A synthetic version of this peptide, referred to as P4, has the sequence: A1G2P3C4I5L6L7A8R9D10R11C12P13G14, and binds to its selecting antibody with a Kd of 42 nM. NMR data indicate that proline-13 is present in both cis and trans configurations, and that these two geometries dramatically affect the overall tertiary structure of the molecule. The peptide lacking this proline binds severalfold better to the ACA, consistent with at least one of these structures having low affinity for binding ACA. Replacement of the arginine-9 position with a proline decreases binding affinity to ACA 10-fold. Another phage library-selected peptide has a proline in position 9, but also has a leucine in position 5, instead of isoleucine. Since its affinity for ACA is nearly as good as that for peptide P4, the phage library screening must have selected for a non-beta-branched amino acid in this position to compensate for the adverse effects of the arginine-9 to proline-9 substitution. The solution structure of a modified version of the antibody-selected phage peptide P4 with the central proline was determined. This peptide has one turn comprised of Ala-Pro-Asp-Arg, with the proline peptide bond in the cis configuration, and another turn that contains the disulfide and adjacent residues. If the disulfide is replaced by a thioether, and the central proline by an alpha-methyl proline, in an attempt to make the peptide more biologically stable, there is little adverse effect on affinity for ACA. The thioether bond/turn is fairly well defined with a Calpha to Calpha separation of 4.9 +/- 0.8 A. The alpha-methyl proline adopts the trans configuration, and this central Ala-(alpha-methyl-Pro)-Asp-Arg turn adopts a distorted type I turn conformation with a probable i to i+3 hydrogen bond. Modeling studies suggest that the proline peptide bond configuration switched from cis to trans in the presence of the alpha-methyl group on proline because of steric hindrance with the beta-carbon of the preceding residue. Overall, this peptidomimetic molecule is structurally very similar to the peptide with natural amino acids, with an rmsd difference of only 1.37 A, when comparing backbone atoms.

Relative risk of post‐transplant renal thrombosis in patients with antiphospholipid antibodies1

IntroductionAntiphospholipid antibody syndrome (APAS) is a condition associated with recurrent arterial and venous thrombosis, recurrent abortions, and thrombocytopenia either with or without lupus. In this study we have evaluated the impact of APAS on the renal transplant outcome of 174 patients.MethodPatients' APAS status was determined by the presence of anticardiolipin antibodies (ACA) and a history of clotting disorders. Serum samples from each patient were tested for the presence of ACA by the ELISA method. Transplant outcomes were monitored for 1 yr.ResultsOf 174 patients, 78 received renal transplants. Six of these 78 patients had APAS as evidenced by either recurrent microrenal angiopathy (2 patients), thrombocytopenia (1 patient) or frequent A‐V shunt thrombosis (3 patients) along with high titers of ACA of IgM, IgG, or both subtypes at the time of their transplants. Each of these 6 patients thrombosed their renal allografts within a week of their transplants. The other 72 transplanted patients with no APAS were all doing well ≥1 yr post‐transplant. The association between APAS and post‐transplant renal thrombosis among these patients is highly significant (p &lt;0.0001). In contrast, no association was discerned between post‐transplant thrombosis and prior sensitization to HLAConclusionOur data demonstrates that patients with APAS are at high risk for development of post‐transplant renal thrombosis.

Is Sydenham's chorea an antiphospholipid syndrome?

In 1686, Thomas Sydenham described a syndrome of chorea occurring in youth which was subsequently shown to be a complication of rheumatic fever. An association between chorea and antiphospholipid antibodies has been reported since 1985. We report two females presenting with chorea, aged 17 and 22, who fulfilled the Jones' criteria for rheumatic fever and concurrently had antiphospholipid antibodies detected in serum. A third patient presented at the age of 16 with two bouts of Sydenham's chorea; no assays for antiphospholipid antibodies were performed at the time but 13 years later she was found to have high titres of anticardiolipin antibodies. No patient had abnormalities in the basal ganglia detected on magnetic resonance imaging. Sydenham's chorea may be part of the spectrum of antiphospholipid-associated neurological disease.

Enhanced Lipid Peroxidation in Patients Positive for Antiphospholipid Antibodies

AbstractThe mechanism leading to the formation of antiphospholipid antibodies (aPL) is still unknown. Because an in vitro study suggested that aPL may derive from pro-oxidant conditions, we sought a relationship between aPL and isoprostanes, indices of lipid peroxidation in vivo. Thirty patients with systemic lupus erythematosus have been studied. Seventeen (56.6%) were positive for aPL because they had lupus anticoagulant and/or high titer of anticardiolipin antibodies (aCL). Plasma levels of tumor necrosis factor (TNF ) and urinary excretion of two isoprostanes, 8-epi-PGF2α and IPF2α -I, free radical catalyzed oxidation products of arachidonic acid, were measured. Patients with systemic lupus erythematosus had higher urinary excretion of 8-epi-PGF2α and IPF2α -I than controls; urinary excretion of the two isoprostanes was highly correlated (Rho = 0.74, P < .0001). Urinary 8-epi-PGF2α was highly correlated with both aCL titer (Rho = 0.70, P < .0001) and TNF (Rho = 0.84, P < .0001), a measure of disease severity. Excretion of this isoprostane was also higher in those patients who exhibited aPL (P < .0001). Comparable correlations were observed with the isoprostane IPF2α -I. No difference of 8-epi-PGF2α was observed between patients with and without previous history of thrombosis. This study, showing the existence of a close association between aPL and increased in vivo lipid peroxidation, supports the hypothesis that these antibodies may result from pro-oxidative conditions and suggests that inflammation may play an important role.